Introduction Bladder cancer (BCa) is the 10th most common type of cancer worldwide, and human papillomavirus (HPV) is the most common sexually transmitted infection. However, the relationship between HPV infection and the risk of BCa is still controversial and inconclusive. Methods This systematic review and meta‐analysis were conducted following the PRISMA 2020 reporting guideline. This study searched four bibliographic databases with no language limitation. The databases included PubMed (Medline), EMBASE, Cochrane Library, and Web of Science. Studies evaluating the interaction between HPV infection and the risk of BCa from inception through May 21, 2022, were identified and used in this study. This study estimated the overall and type‐specific HPV prevalence and 95% confidence intervals (95% CI) using Random Effects models and Fixed Effects models. In addition, this study also calculated the pooled odds ratio and pooled risk ratio with 95% CI to assess the effect of HPV infection on the risk and prognosis of bladder cancer. Two‐sample mendelian randomization (MR) study using genetic variants associated with HPV E7 protein as instrumental variables were also conducted. Results This study retrieved 80 articles from the four bibliographic databases. Of the total, 27 were case–control studies, and 53 were cross‐sectional studies. The results showed that the prevalence of HPV was 16% (95% CI: 11%–21%) among the BCa patients, most of which were HPV‐16 (5.99% [95% CI: 3.03%–9.69%]) and HPV‐18 (3.68% [95% CI: 1.72%–6.16%]) subtypes. However, the study found that the prevalence varied by region, detection method, BCa histological type, and sample source. A significantly increased risk of BCa was shown for the positivity of overall HPV (odds ratio [OR], 3.35 [95% CI: 1.75–6.43]), which was also influenced by study region, detection method, histological type, and sample source. In addition, the study found that HPV infection was significantly associated with the progression of BCa (RR, 1.73 [95% CI: 1.39–2.15]). The two‐sample MR analysis found that both HPV 16 and 18 E7 protein exposure increased the risk of BCa (HPV 16 E7 protein: IVW OR per unit increase in protein level = 1.0004 [95% CI: 1.0002–1.0006]; p = 0.0011; HPV 18 E7 protein: IVW OR per unit increase in protein level = 1.0003 [95% CI: 1.0001–1.0005]; p = 0.0089). Conclusion In conclusion, HPV may play a role in bladder carcinogenesis and contribute to a worse prognosis for patients with BCa. Therefore, it is necessary for people, especially men, to get vaccinated for HPV vaccination to prevent bladder cancer.

Background: Ferroptosis is a unique iron-dependent form of cell death and bladder cancer (BCa) is one of the top ten most common cancer types in the world. However, the role of ferroptosis in shaping the tumor microenvironment and influencing tumor clinicopathological features remains unknown.Methods: Using the data downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we comprehensively evaluated the ferroptosis patterns of 570 BCa samples based on 234 validated ferroptosis genes reported in the FerrDb database and systematically correlated these ferroptosis patterns with tumor microenvironment (TME) cell-infiltrating characteristics. The ferroptosis score was constructed to quantify ferroptosis patterns of individuals using principal component analysis (PCA) algorithms.Results: Four distinct ferroptosis patterns and two gene clusters were finally determined. Significant differences in clinical characteristics and the prognosis of patients were found among different ferroptosis patterns and gene clusters, so were in the mRNA transcriptome and the landscape of TME immune cell infiltration. We also established a set of scoring system to quantify the ferroptosis pattern of individual patients with BCa named the ferroptosis score, which was discovered to tightly interact with clinical signatures such as the TNM category and tumor grade and could predict the prognosis of patients with BCa. Moreover, tumor mutation burden (TMB) was positively correlated to the ferroptosis score, and the low ferroptosis score was related to a better response to immunotherapy using PD-1 blockade. Finally, we also found there existed a positive correlation between the sensitivity to cisplatin chemotherapy and ferroptosis score.Conclusions: Our work demonstrated and interpreted the complicated regulation mechanisms of ferroptosis on the tumor microenvironment and that better understanding and evaluating ferroptosis patterns could be helpful in guiding the clinical therapeutic strategy and improving the prognosis of patients with BCa.

Background. Renal cell carcinoma (RCC) is one of the most common aggressive malignant tumors in the urinary system, among which the clear cell renal cell carcinoma (ccRCC) is the most common subtype. The immune-related long noncoding ribonucleic acids (irlncRNAs) which are abundant in immune cells and immune microenvironment (IME) have potential significance in evaluating the prognosis and effects of immunotherapy. The signature based on irlncRNA pairs and independent of the exact expression level seems to have a latent predictive significance for the prognosis of patients with malignant tumors but has not been applied in ccRCC yet. Method. In this article, we retrieved The Cancer Genome Atlas (TCGA) database for the transcriptome profiling data of the ccRCC and performed coexpression analysis between known immune-related genes (ir-genes) and lncRNAs to find differently expressed irlncRNA (DEirlncRNA). Then, we adopted a single-factor test and a modified LASSO regression analysis to screen out ideal DEirlncRNAs and constructed a Cox proportional hazard model. We have sifted 28 DEirlncRNA pairs, 12 of which were included in this model. Next, we compared the area under the curve (AUC), found the cutoff point by using the Akaike information criterion (AIC) value, and distinguished the patients with ccRCC into a high-risk group and a low-risk group using this value. Finally, we tested this model by investigating the relationship between risk score and survival, clinical pathological characteristics, cells in tumor immune microenvironment, chemotherapy, and targeted checkpoint biomarkers. Results. A novel immune-related lncRNA pair signature consisting of 12 DEirlncRNA pairs was successfully constructed and tightly associated with overall survival, clinical pathological characteristics, cells in tumor immune microenvironment, and reactiveness to immunotherapy and chemotherapy in patients with ccRCC. Besides, the efficacy of this signature was verified in some commonly used clinicopathological subgroups and could serve as an independent prognostic factor in patients with ccRCC. Conclusions. This signature was proven to have a potential predictive significance for the prognosis of patients with ccRCC and the efficacy of immunotherapy.

Purpose. To clarify the efficiency and outcomes of suctioning ureteral access sheath (UAS) during flexible ureteroscopic lithotripsy (fURL) for the management of renal stones. Methods. Between January 2017 and January 2019, a total of 444 patients with renal stones undergoing fURL were divided into suctioning UAS and nonsuctioning UAS groups. The outcomes of patients in both groups were compared using a matched-pair analysis (1 : 1 scenario). Furthermore, a directed acyclic graph (DAG) was drawn to guide the multivariate logistic regression model and analyze the protective effect of suctioning UAS on the incidence of postoperative systemic inflammatory response syndrome (SIRS). Results. Before propensity score matching, significant differences were observed between the two groups in blood white cell counts, urine white cell counts, preoperative fever, preoperative indwelling stents, and laterality ( P < 0.05 ). Eighty-one patients in the suctioning UAS group were successfully matched with 81 patients in the nonsuctioning group. The stone-free rate (SFR) on postoperative day 1 after fURL in the suctioning group was higher than that in the nonsuctioning group (86.4% vs. 71.6%; P = 0.034 ), whereas it was comparable between the two groups 1 month after the surgery (88.9% vs. 82.7%; P = 0.368 ). The incidence of postoperative fever or SIRS was lower in the suctioning group (fever: 3.70% vs. 14.8%; P = 0.030 ; SIRS: 1.23% vs. 12.3%; P = 0.012 ). However, the operative duration was similar in both groups (mean (SD)) (72.9 (28.1) min vs. 80.0 (29.5) min; P = 0.121 ). The result of the multivariate logistic regression model guided by DAG revealed that the application of nonsuctioning UAS (odds ratio: 5.28 [1.38–35.07], P = 0.034 ) during fURL was associated with postoperative SIRS. Conclusions. The application of suctioning UAS during fURL was associated with higher SFR on day 1 after surgery and a lower incidence of postoperative fever or SIRS.

BackgroundSUMOylation is an important component of post-translational protein modifications (PTMs), and bladder cancer (BCa) is the ninth most common cancer around the world. But the comprehensive role of SUMOylation in shaping tumor microenvironment (TME) and influencing tumor clinicopathological features and also the prognosis of patients remains unclear.MethodsUsing the data downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), we comprehensively evaluated the SUMOylation patterns of 570 bladder cancer samples, and systematically correlated these SUMOylation patterns with TME immune cell infiltrating characteristics. The SUMO score was constructed to quantify SUMOylation patterns of individuals using principal component analysis (PCA) algorithms.ResultsTwo distinct SUMOylation patterns and gene clusters were finally determined. Significant differences in the prognosis of patients were found among two different SUMOylation patterns and gene clusters, so were in the mRNA transcriptome and the landscape of TME immune cell infiltration. We also established a set of scoring system named SUMO score to quantify the SUMOylation pattern of individuals with BCa, which was discovered to be tightly connected with tumor clinicopathological characteristics and could predict the prognosis of patients with BCa. Moreover, SUMO score was a considerable predictive indicator for the survival outcome independent of tumor mutation burden (TMB) and low SUMO score was related to better response to immunotherapy using PD-1 blockade. We also found that there existed a significant relationship between sensitivity to commonly used chemotherapy drugs and SUMO score. Finally, a nomograph based on five features, namely, SUMO score, age, gender, T category, and M category was constructed to predict the survival probability of patients with BCa in 1, 3, and 5 years, respectively.ConclusionsOur work demonstrated and overviewed the complicated regulation mechanisms of SUMOylation in bladder cancer, and better understanding and evaluating SUMOylation patterns could be helpful in guiding clinical therapeutic strategy and improving the prognosis of patients with BCa.

Background. Urolithiasis is common worldwide and can predispose to urinary tract infections and renal failure. We aimed to explore the global, regional, and national burden of urolithiasis between 1990 and 2019, stratified by sex, age, and sociodemographic index (SDI). Methods. From 1990 to 2019, data on the number of incident cases of urolithiasis, associated deaths, and disability-adjusted life years (DALYs) were extracted from the 2019 Global Burden of Disease (GBD) study. The trends for the incidence rate, mortality, and DALYs were evaluated using estimated annual percentage changes (EAPCs). Results. The incidence of urolithiasis increased by 48.57%, from 77.78 million incident cases in 1990 to 115.55 million in 2019, while its age-standardized incidence rate (ASIR) decreased. The ASIR increased slightly in the low SDI regions (EAPC = 0.33; 95% confidence interval [CI]: 0.24–0.43), while ASIRs in other SDI regions decreased. The incidence of urolithiasis by age presented a unimodal distribution, with the peak observed in patients aged between 50 years and 70 years. Urolithiasis-related mortality and DALYs also increased over time. Yet, the age-standardized death rate (ASDR) decreased by 2.05% (95% CI, −2.25% to −1.85%) per year, and the annual age-standardized DALY rate decreased by 1.77% (95% CI, −1.92% to −1.63%). The mortality and DALYs increased with age. The incidence, mortality, and DALYs were greater in males than those in females. The burden of urolithiasis showed obvious differences in its regional distribution over the past three decades. Conclusion. From 1990 to 2019, ASIR, ASDR, and age-standardized DALY rate of urolithiasis have decreased. Yet, particularly significant differences exist in the geographic, age, and sex distribution. Thus, medical resources should be rationally allocated and adjusted according to the geographic and demographic distribution of urolithiasis.

The prognosis of bladder cancer patients is strongly related to both the immune-infiltrating cells and the expression of lncRNAs. In this study, we analyzed the infiltration of immune cells in 403 bladder cancer samples obtained from TCGA by applying the ssGSEA to these samples, then dividing them into high/low immune cell infiltration groups. Based on these groupings, we found 404 differentially expressed immune infiltration-related lncRNAs, which were successively analyzed by univariate Cox regression, then Least Absolute Shrinkage and Selection Operator (LASSO), and finally stepwise multiple Cox regression. Then 12 differentially expressed immune infiltration-related lncRNAs were identified and used to construct a prognostic signature for bladder cancer. Subsequently, Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, and multivariate time-dependent ROC analyses (for 1, 3, 5 years) all revealed that this signature performed well in predicting overall survival and served as an independent prognostic factor for patients with bladder cancer. Finally, both TIMER and CIBESORT showed that this 12-lncRNA prognostic signature for bladder cancer was associated with the infiltration of immune cell subtypes. Besides, nomogram considered risk score and clinical characteristics was assembled and showed great performance. More importantly, we found our signature could well distinguish the drug response of patients with bladder cancer. High risk patients showed a better response to cisplatin, doxorubicin, and anti-CTLA4 immunotherapy, low risk patients showed a better response to methotrexate and anti-PD1 immunotherapy compared with each other.

Bladder cancer (BCa) is the 10th most commonly diagnosed cancer worldwide, and cellular senescence is defined as a state of permanent cell cycle arrest and considered to play important roles in the development and progression of tumor. However, the comprehensive effect of senescence in BCa has not ever been systematically evaluated. Using the genome-wide CRISPR screening data acquired from DepMap (Cancer Dependency Map), senescence genes from the CellAge database, and gene expression data from The Cancer Genome Atlas (TCGA), we screened out 12 senescence genes which might play critical roles in BCa. A four-cell-senescence-regulator-gene prognostic index was constructed using the least absolute shrinkage and selection operator (LASSO) and multivariate COX regression model. The transcriptomic data and clinical information of BCa patients were downloaded from TCGA and Gene Expression Omnibus (GEO). We randomly divided the patients in TCGA cohort into training and testing cohorts and calculated the risk score according to the expression of the four senescence genes. The validity of this risk score was validated in the testing cohort (TCGA) and validation cohort (GSE13507). The Kaplan–Meier curves revealed a significant difference in the survival outcome between the high- and low-risk score groups. A nomogram including the risk score and other clinical factors (age, gender, stage, and grade) was established with better predictive capacity of OS in 1, 3, and 5 years. Besides, we found that patients in the high-risk group had higher tumor mutation burden (TMB); lower immune, stroma, and ESTIMATE scores; higher tumor purity; aberrant immune functions; and lower expression of immune checkpoints. We also performed gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) to investigate the interaction between risk score and hallmark pathways and found that a high risk score was connected with activation of senescence-related pathways. Furthermore, we found that a high risk score was related to better response to immunotherapy and chemotherapy. In conclusion, we identified a four-cell-senescence-regulator-gene prognostic index in BCa and investigated its relationship with TMB, the immune landscape of tumor microenvironment (TME), and response to immunotherapy and chemotherapy, and we also established a nomogram to predict the prognosis of patients with BCa.